The objective of this research is to study the viral and cellular control of the association between viral and host DNA in cells transformed by Polyoma virus. We also want to study the contribution that each viral early protein makes to the altered phenotype of Polyoma transformed cells. Our work is planned along three main lines of Research: 1) The study of the mechanism of integration, excision and amplification of polyoma genomes. In Polyoma transformed cells excision and amplification of integrated viral DNA sequences can occur at a high rate, and these phenomena require viral large T-Antigen and involve homologous recombination. We want to understand the mechanism by which large T-Ag promotes excision and amplification and whether it can influence rearrangements of genes unlinked to Polyoma DNA sequences. In addition, we will also study the modalities of the initial integration event and the role of replication of recombination in the formation of tandem insertions. 2) The study of the factors which contribute to the evolution of integrated viral DNA sequences in Polyoma transformed cells and which lead to selection against large T-Ag function. 3) The study of the contribution of the three Polyoma early proteins to the determination of the altered properties of transformed cells both in continuous cell lines primary embryo cultures.